1. Field
The invention relates generally to blood filtration and to continuous renal replacement therapy (CRRT). More specifically, the invention relates to monitoring fluid loss and fluid replacement during CRRT therapy and automatically controlling fluid flow rates to achieve a desired balance.
2. Background
Extracorporeal blood treatment therapy is widely used for critically ill patients. Many of these patients suffer from acute renal failure and are treated in an Intensive Care Unit (ICU) with various forms of hemofiltration, known generally as Continuous Renal-Replacement Therapy (CRRT). Many different CRRT techniques are used today, including Continuous Veno-Venous Hemofiltration (CVVH), Continuous Arterio-Venous Hemofiltration (CAVH), and Continuous Veno-Arterial Hemofiltration (CVAH). In hemofiltration, blood from a patient is directed into an extracorporeal circuit and made to flow under pressure through a blood filter, or hemofilter. The hemofilter contains a semi-permeable membrane that separates water and waste solutes from the main flow of blood. The filtered blood is then returned to the patient.
Another form of renal replacement therapy that can be used for patients with renal failure in Intensive Care Units (ICUs) is hemodialysis. Hemodialysis differs from hemofiltration in that a specially formulated dialysate fluid is made to flow along a side of the semi-permeable membrane opposite to the side where blood flows. Concentration gradients across the membrane encourage the migration of unwanted solutes away from the blood into the dialysate by osmosis.
Hemodialysis usually can only be applied for a few hours per day, and as such, is more restrictive and sometimes less effective than pure hemofiltration. However, hemodialysis can be combined with hemofiltration to provide more complex blood filtration therapies. Examples of such combined techniques are Continuous Veno-Venous Hemodiafiltration (usually abbreviated as CVVHD or CVVHDF) and Continuous Arterio-Venous Hemodiafiltration (usually abbreviated as CAVHD or CAVHDF).
Typically, a hemofilter, or artificial kidney is used during CRRT therapy. The artificial kidney may be formed of hollow-fibers or closely separated plates, and is connected to a patient's bloodstream through an extracorporeal circuit. In CVVHD, the supply from and return to the blood of the patient is made via two venous accesses, using a blood pump to provide the driving force for the transport of blood from the patient into the artificial kidney and back to the patient. In CAVHD, the access which provides the supply of blood to the artificial kidney is made through an artery, and the return of the blood to the patient is made through a vein. Thus, blood pumps are not generally used in CAVHD because the arterial blood pressure provides the driving force to transport the blood. Because a pump provides better control of blood flow, and because CVVHD avoids arterial catheter-related complications, CVVHD is a preferred renal replacement therapy in ICUs over CAVHD.
In CVVHD, the patient's blood is passed through the artificial kidney over a semipermeable membrane. The semipermeable membrane selectively allows plasma water and matter in the blood to cross the membrane from the blood compartment into the filtrate compartment, mimicking the natural filtering function of a kidney. This leads to a considerable loss of fluid from the blood, which is removed as the filtrate in the artificial kidney. Every liter of filtrate fluid that is removed in the artificial kidney contains a large fraction of the molecules that are dissolved in the plasma, such as urea, creatinine, phosphate, potassium, sodium, glucose, amino acids, water-soluble vitamins, magnesium, calcium, sodium, and other ions and trace elements. The fraction of molecules that pass the semipermeable membrane depends on the chemical characteristics of the molecules, the structure of the membrane, and the transmembrane pressure (TMP). In order to keep the blood volume of the patient constant, a substitution fluid may be added to the bloodstream in the extracorporeal circuit downstream of the artificial kidney and upstream of the venous return catheter.
In a normal CVVHD procedure, approximately 50 liters of filtrate are removed per 24 hours, and approximately the same amount of substitution fluid is added to the bloodstream. The substitution fluid commonly used is conventional infusion fluid comprising a physiological saline solution generally containing about 140 mmol/L of sodium ions, 1.6 mmol/L of calcium ions, 0.75 mmol/L of magnesium ions, 36 mmol/L of bicarbonate ions, and 110 mmol/L of chloride ions.
In modern ICU settings, performing any type of CRRT requires the use of a CRRT machine for controlling blood flow through an extracorporeal circuit. Typically, a CRRT machine draws blood from a patient through an access line using a blood pump (e.g., a peristaltic pump), and returns the blood to the patient through a return line. The flow rate of the blood pump, the design of the artificial kidney, and the type of CRRT therapy used, determines the fluid loss rate from the bloodstream through the filter.
Pressure sensors throughout the extracorporeal circuit may be used to sense and alarm fluid flow at various points. For example, an access line pressure sensor may sense pressure of blood entering the extracorporeal circuit, and generate an alarm in the event the sensor senses an out-or-range condition. Similarly, a return line pressure sensor may also sense and transmit pressure signals and generate alarms. Pressure sensors placed before the hemofilter, in the filtrate outflow, and in the return line provide measurements needed to calculate TMP or the pressure drop (PD) in blood flowing through the artificial kidney. CRRT machines may also include other protective features such as air bubble traps, air bubble detectors, and automatic clamps to prevent air bubble migration through the return line and back to the patient. Anticoagulation additives such as heparin or citrates may also be added to the circuit using more complex processes.
In a technique known as Slow Continuous Ultra-Filtration (SCUF) therapy, a filtration pump can be used to remove plasma water (ultrafiltrate or UF) from the blood circulating into the artificial kidney. The UF is typically collected inside a filtration container and continuously weighed by a filtration scale. In CVVH therapy, a filtration pump may be used to remove UF from the blood circulating into the artificial kidney and to direct the UF to a filtration container. In both of these therapies, a substitution fluid or replacement fluid is typically injected into the circulating blood to make up for fluid loss through the artificial kidney. The substitution fluid may be added as a pre-dilution supplement or a post-dilution supplement. When added as a pre-dilution supplement, the substitution fluid is injected upstream of the hemofilter. When added as a post-dilution supplement, the substitution fluid is injected downstream of the hemofilter. In both cases, injection of the substitution fluid may be effected by a separate substitution pump. Some CRRT machines allow both pre-dilution and post-dilution together and therefore are configured with two substitution pumps. The source of substitution fluid is typically a container suspended near the CRRT machine. Some CRRT machines are configured to use one scale for weighing pre-dilution substitution fluid and another scale for weighing post-dilution substitution fluid.
During CVVHD therapy, dialysate fluid flows into the dialysate compartment of the artificial kidney, and a filtration pump is used to remove used dialysate (or effluent) from the blood circulating through the artificial kidney. The effluent is collected inside a filtration container and may also be weighed to monitor fluid loss.
In CVVHDF therapy, a filtration pump is used to remove UF from the blood circulating through the artificial kidney. The UF may also be collected in a filtration container and weighed. Substitution fluid (pre-dilution or post-dilution) and dialysate may also be provided and periodically weighed. CRRT machines have been configured using a separate scale for weighing dialysate fluid, and using a separate or common scale for weighing pre-dilution and post-dilution fluids.
All of the above therapies may include a procedural safeguard where UF or plasma fluid lost through the artificial kidney can be compared to the amount of substitution fluid added to the extracorporeal circuit. The difference yielded by this comparison is the total fluid loss (or gain) TFL. In most therapies, TFL is ideally maintained at zero, i.e., no net loss of vital fluids.
There are two common techniques for detecting TFL in CRRT machines: direct regulation and differential regulation.
Direct regulation calculates TFL by reading weight values for both filtration fluid and substitution fluid at regular time intervals. The weighed value of filtration fluid is compared to an expected value of filtration fluid calculated by the CRRT machine. Any difference between weighed and expected values yields a correction signal that adjusts filtration flow rate caused by the filtration pump. Similarly, the weighed value of substitution fluid is compared to an expected value of substitution fluid calculated by the CRRT machine. Any difference between weighed and expected values yields a correction signal that adjusts substitution flow rate caused by the substitution pump. In this manner, the performance of each pump is individually controlled to meet predetermined performance criteria.
Differential regulation calculates TFL by continuously measuring weight change of filtration and substitution fluids over the same time period. The change in filtration fluid in a single period is subtracted from the change in substitution fluid over the same time period, yielding a value for TFL. This value is compared to a predetermined value of expected TFL. If the comparison yields a difference, a correction signal is generated to balance the system, i.e., to govern one or both of the filtration and substitution pump flow rates and cause TFL to converge toward zero or some other desired value.
Both direct and differential regulation schemes have limitations. When regulation cannot achieve a desired balance, an alarm may be generated. The alarm setpoint is typically fixed by the manufacturer of the CRRT machine. Often the alarm setpoint is fixed at around 50 g when treating adult patients, and at around 20 g when treating pediatric patients. This alarm is commonly known as a “balance alarm”.
When a balance alarm occurs, the treatment pumps (substitution, dialysate and/or filtration pumps) stop. In such a case, the system will remain inoperative until the user (e.g., a health care professional) identifies the cause of the alarm, rectifies the problem, and restarts the CRRT machine. However, restarting the CRRT machine reinitializes the system without recognizing that the patient has experienced a fluid imbalance equivalent to the balance alarm setpoint. In other words, the CRRT machine (treating an adult patient) will restart without accounting for a pre-existing plus-or-minus 50 g fluid imbalance, and unfortunately attempt to maintain that same imbalance throughout the therapy.
If the user fails to solve the underlying problem that drives the system into an unbalanced condition before restarting the system, serious hemodynamic instability can result. When the CRRT machine is restarted, a second balance alarm may occur a short time later. Then, after a subsequent restart, an additional error equal to the setpoint value will be added to the first error. As errors accumulate in this manner, fluid level in a patient can become dangerously imbalanced while the CRRT machine indicates normal operating conditions. For example, restarting 10 times without resolving the underlying control problem could generate a 500 g increase or decrease in fluid level. In an ICU setting, such hemodynamic instability could be fatal.